DNA tetraplex formation in the control region of c-myc.
The c-myc oncogene is one of the most commonly malfunctioning genes in human cancers, and is an attractive target for anti-gene therapy. Although synthetic oligonucleotides designed to silence c-myc expression via one of its major control elements function well in vitro, their mode of action has been indefinite. Here we show that the targeted control element adopts an intrastrand fold-back DNA tetraplex, which requires potassium ions for stability in vitro. We believe formation of the tetraplex is important for c-myc activation in vivo, and propose a transcription initiation mechanism that explains how anti-gene therapy silence c-myc at the molecular level.
Simonsson
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T
Department of Biochemistry, Lundberg Institute, Chalmers University of Technology, Medicinaregatan 9C, SE-413 90 Goteborg, Sweden. tomas@bcbp.chalmers.se
Pecinka
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Kubista
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D001483:Base Sequence; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D004355:Drug Stability; D005786:Gene Expression Regulation; D016259:Genes, myc; D006801:Humans; D066298:In Vitro Techniques; D008957:Models, Genetic; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D011188:Potassium / Q000737:chemistry
D009838:Oligodeoxyribonucleotides; D004247:DNA; D011188:Potassium